Composition for preventing, or precaution for dry eye

ABSTRACT

As another aspect of the present invention, a composition for prevention or improvement of dry eye syndrome, dryness of eye, and stiff neck and shoulder, comprises freeze-dried bilberry fruit extract.

TECHNICAL FIELD

The present invention relates to a composition, which includes bilberry extract, for prevention and/or improvement of at least one of dry eye syndrome, dryness of eye, and stiff neck and shoulder.

RELATED ART

Bilberry (Vaccinium myrtillus) is a small fruit tree of Vaccinium of Ericaceae. It is a wild species and mainly grows naturally in Northern Europe.

Bilberry fruits are popular as juice and jam for a long time. Especially, in Europe, functions of bilberry fruits are actively studied. Bilberry includes anthocyanin which is one of polyphenols. There are many reports that the anthocyanin has many bioactivities such as antiangiogenic effect, antibacterial effect, antidiabetic effect, antitumor effect, and anti-obesity effect.

Incidentally, in recent years, working time with Visual Display Terminals (VDT) becomes longer by the development of information technology.

Here, “VDT work” means that the work in which VDT such as a display and a key board are used.

In VDT work, it is reported that the number of times of eye blinking becomes decreased (see Non-patent literature 1) and dryness of eye is induced by incomplete blinking (see Non-patent literature 2).

Especially, many of light sources used in VDT work are light-emitting diodes (LED). It is reported that generation of active oxygen is occurred by overexposure of blue-light which is emitted from the LED (Non-patent literature 3,4).

Then, it is thought that the active oxygen is the origin of asthenopia, dry eye syndrome, and/or dryness of eye.

Non-Patent Literature

-   [Non-patent literature 1] Tsubota K, Nakamori K. “Dry eyes and video     display terminals.”, N Engl J Med. 1993; 328: 584. -   [Non-patent literature 2] Himebaugh N, Begley C, Bradley A,     Wilkinson J. “Blinking and tear break-up during four visual tasks.”,     Optom Vis Sci. 2009; 86: E106-14. -   [Non-patent literature 3] Tosini G, Ferguson I, Tsubota K. “Effects     of blue light on the circadian system and eye physiology.” Molecular     Vision. 2016; 22:61-72. -   [Non-patent literature 4] Kuse Y, Ogawa K, Tsuruma K, Shimazawa M,     Hara H., “Damage of photoreceptor-derived cells in culture induced     by light emitting diode-derived blue light.”, Sci Rep., 2014; 4:     5223.

DESCRIPTION OF THE INVENTION Problems to be Solved by the Invention

Incidentally, it is thought that anthocyanin derived from blueberry may be effective for asthenopia.

However, the correlation between extract of bilberry-fruits and the efficacy of dry eye syndrome and/or dryness of eyes is not clear.

Further, in an aspect of economy, it is desirable that effects can be obtained with less intake.

The less intake of anthocyanin brings reducing the cost of commodities, and it is possible to provide commodities with lower cost for consumers.

Then, in consideration of the above-mentioned problem, the objection of the present invention is to provide a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiffness, which contains bilberry fruit extract and is effective with less intake.

Solution to the Problems

From research of bilberry fruit extract, the inventors found that freeze-dried bilberry fruit extract can improve dry eye syndrome, dryness of eye and/or stiff neck and shoulder.

Thus, a composition of one aspect of the present invention is for prevention and/or improvement of dry eye syndrome and/or dryness of eye, and the composition contains freeze-dried bilberry fruit extract.

Further, a composition of another aspect of the present invention is for prevention and/or improvement of stiff neck and shoulder, and the composition contains freeze-dried bilberry fruit extract.

Thus, a composition of one aspect of the present invention is for prevention and/or improvement of dry eye syndrome, dryness of eye, and/or stiff neck and shoulder, and the composition contains freeze-dried bilberry fruit extract.

Further, a method for producing a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiff neck and shoulder, which is another aspect of the present invention, comprises a step of obtaining bilberry extract by using water-containing ethanol, and a step of freeze-drying the bilberry extract.

Effects of the Invention

Thus, by the present invention, it is possible to provide a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiff neck and shoulder, which includes bilberry fruit extract and is effective with less intake.

BEST MODE FOR CARRYING OUT THE PRESENT INVENTION

Hereafter, embodiments of the present invention will be described. However, the present invention can be carried out with many other embodiments and is not limited to embodiments described below.

A composition of one aspect of the embodiment of the present invention (hereafter “the composition”) comprises bilberry fruit extract which is freeze-dried.

In the composition, “bilberry-fruit extract” is the extract that is extracted from bilberry (botanical name: Vaccinium mytrillus L., English name: Bilberry).

It is desirable that a raw material for the bilberry fruit extract is such as a plant itself, a dried-fruit, a ground product, a puree, or a raw fruit juice.

Further, the bilberry fruit extract can be obtained by solvent extraction from a raw material itself or a processed material which is properly processed.

The extract includes such as a filtrate which is obtained by filtering the extract, a concentrated material which is obtained from the extract by removing a solvent and being concentrated, a purified product which is obtained by removing impurities from the extract, and a solid material which is obtained from those liquids by evaporating the liquid component.

The method for concentrating the extract is adoptable such as evaporative concentration and membrane concentration, but it is not limited to them.

Further, the method for purifying can be carried out using at least one of means such as a synthetic adsorption resin, an activated carbon, an ion-exchange resin, a gel filter material such as sephadex and bio-gel, chromatography, and recrystallization.

Further, here, it is desirable that the solvent which is used in solvent extraction comprises at least one of water, alcohol and glycerin. Further, water-containing alcohol is more desirable. But it is not limited to them.

Here, it is desirable that the alcohol comprises at least one of methanol, ethanol, propanol, isopropanol and butanol, and it is more desirable that the alcohol comprises ethanol. But it is not limited to them, too.

In the case of water-containing ethanol, it is desirable that ethanol is included 20 wt % or more and 99 wt % or less. Moreover, 40 wt % or more and 90 wt % or less is more desirable, and 60 wt % or more and 90 wt % or less is the most desirable.

Further, the bilberry fruit extract of the composition is freeze-dried composition.

In this embodiment, the method of freeze-drying comprises a freezing step in which the bilberry fruit extract is frozen rapidly at low temperature, and a drying step in which the frozen extract is dried with pressure reduction. But it is limited to them.

In the drying step, as a realistic range, it is desirable that the freezing temperature is −10 degree Celsius or less and −50 degree Celsius or more. But, it is not limited to it as long as it is possible to freeze bilberry fruit extract.

Further, in the step, it is desirable that the freezing rate is rapid for maintaining uniform dispersion state of the bilberry fruit extract. Concretely, it is desirable that the freezing rate is −5 degree Celsius per hour or more and −20 degree Celsius per hour or less.

Further, in this case, it is desirable that the concentration of solid content of the bilberry fruit extract is 5 wt % or more and 50 wt % or less, 10 wt % or more and 40 wt % or less is more desirable, and 30 wt % is especially desirable. But it is not limited to them as long as it is possible to freeze the extract.

Further, low concentration is desirable because it is easy to obtain smaller particles.

Further, in the step of drying with pressure reduction, it is desirable that the step comprises a step of reducing pressure at room temperature, and a step of heat-drying at the reduced pressure.

Here, it is desirable that the length of time of the pressure reduction is 10 hours or more and 50 hours or less. But it is not limited to it as long as it is possible to dry the extract.

Further, it is desirable that the temperature of heat-drying is 20 degree Celsius or more and 50 degree Celsius or less, and 40 degree Celsius or less is more desirable. But it is not limited to it. Within the above-mentioned range, it is possible to obtain extract particles efficiently with reducing decomposition of active ingredient.

Further, it is desirable that the time of heating is 1 hour or more and 10 hours or less.

In this embodiment, since the composition is produced by freeze-drying the bilberry fruit extract, it is possible to obtain fruit extract with maintaining active ingredient (anthocyanin) stably.

Further, since it is possible to obtain smaller particles by freeze-drying, it is possible that the extraction rate of the active ingredient is high, and prevention and/or improvement of dry eye syndrome (dryness of eye) with less amount is realized.

On the other hand, in such as spray-drying, as a drying step is carried out with heating, the active ingredient of the bilberry fruit extract is decomposed at high temperature and the effect of the extract will be less.

Further, it is obvious that the color of the bilberry fruit extract which is obtained by freeze-drying is markedly different from the extract which is obtained by other way of drying.

It is thought that, by freeze-drying, the particle size is smaller than that of other ways such as spray-drying, and the extract will be more effective.

Concretely, it is possible to realize that, in particle seize distribution, the 10% particle seize is 4 μm or less. In some cases, it is possible to realize 3 μm or less.

The particle size distribution is measurable by a particle counter.

In the composition, it is considered that the active ingredient is anthocyanin which is extracted from bilberry.

It is desirable that the anthocyanin extracted from bilberry is contained 30 wt % or more and 50 wt % or less in the composition. And it is more desirable that the anthocyanin is contained 35 wt % or more and 50 wt % or less.

Further, in addition to the above-identified freeze-dried bilberry fruit extract, it is possible that the composition can include such as excipient, coloring material, sweetening agent, and suspending agent.

As an excipient, dextrin is desirable, but it is not limited thereto.

Further, it is desirable that the form of the composition is such as food, medicine or cosmetic.

Especially, in case of food, functional food or health food is desirable.

Moreover, in case of food, it is desirable the state is solid matter or drink.

Further, in the case that the composition is food, the form can be dessert such as a drink, a candy, a jelly, or a gummy candy.

In the case that the composition is health food or functional food, the form can be such as a tablet, a hard capsule, a soft capsule, a granule or a drink.

Further, in the case that the composition is medicine, the form can be such as a tablet, a capsule, a pill, a liquid, or an emulsion.

It is preferable that the method of medication is oral administration, but it is not limited to it.

Further, it is possible to add various support medium, such as an excipient, a coloring agent, a sweetening agent, and a suspending agents, within the pharmaceutically acceptable range.

Further, the content of bilberry-fruit extract in the composition is adjustable for estimated amount of intake, but, in case of a tablet, a capsule or a pill, it is desirable that the content is 10 wt % or more and 95 wt % or less, and it is more desirable that 15 wt % or more.

For obtaining the effect of prevention and/or improvement of dry eye syndrome or dryness of eye, it is good that the amount of intake of bilberry fruit extract is 500 mg per day or less. And then 100 mg per day or more and 400 mg per day is desirable, 300 mg or less is more desirable, and 160 mg per day is the most desirable. If the intake is 120 mg per day or more, it is possible to obtain the effect certainly.

Incidentally, the composition has an effect of prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiff neck and shoulder.

The range which the effect can be obtained will be clear by the below-described examples.

Thus, by the present invention, it is possible to provide a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiff neck and shoulder, which contains bilberry fruit extract and is effective with less intake.

Examples

The effect of the invention was confirmed by producing the composition of above-mentioned embodiment actually. Hereafter, the examples will be concretely described.

(1) Producing Bilberry Fruit Extract

First, frozen fruit of bilberry (Vaccinium myrtillus) was crushed, and water-containing ethanol was added to the crushed bilberry. Then, after extracting, filtrate was obtained.

After concentrating the filtrate and refining which uses resin, purified liquid was obtained.

After concentrating the purified liquid, bilberry fruit extract was obtained.

Then, the concentration which included the bilberry fruit extract (solid content) 30 wt % was frozen at −30 degree Celsius for 5 hours.

And the frozen was put in freeze-drier, and it was dried with decompression to 100 Pa at room temperature.

Additionally, the temperature was risen up to 30 degree Celsius, and the material was dried at 100 Pa which was same as above.

By high performance liquid chromatography, it was found that the amount of anthocyanin in the extract was 36 wt % per the total weight of bilberry fruit extract.

(2) Clinical Test

The test subjects are healthy (but feel eyestrain) Japanese adults who daily play TV games, use computers or smartphones, or do VDT works, for 4 hours or more, and the feel eyestrain.

In the clinical test, test hard capsules, each of which included 40 mg of bilberry fruit extract (14.4 mg of anthocyanin extracted from bilberry was included), were used.

Further, placebo capsules were prepared by filling such as food additives into hard capsules so that the appearances were same as the test hard capsules (test food).

And then, 22 Japanese adults were divided in two groups. One is intervention group and the other is placebo group.

The adults of the intervention group took the bilberry fruit extract 120 mg per day for 6 weeks or 160 mg per day for 6 weeks.

The adults of the placebo group took the placebo capsules for 6 weeks same as them of the intervention group.

And then, result of Schirmer's test, which measures amount of lachrymal fluid, and sensation of dryness of eye and stiff shoulder were evaluated, before taking the extract and after 6 weeks from taking it.

The evaluation of sensation were carried out before taking the extract and at the sixth week after taking it. And further, the evaluation were carried out before VDT load of portable game (60 minutes) and after the VDT load, respectively.

(3) Result of Schirmer's Test when the Amount of Intake was 120 mg Per Day

The length of wet part of the test paper of left eye of the intervention group was increased 80.2% (p=0.037) at the sixth week after taking the extract, and that of right eye was also increased 16.9% (p=0.10). The average was increased 44.5% (p=0.032).

Moreover, by comparison between groups, at sixth week after taking the extract, amount of lachrymal fluid of right eye of the intervention group was significantly increased, compare to the placebo group (p=0.048).

Though similar trend could not be found at the average of right eye and left eye, it was confirmed that the amount of lachrymal fluid of the intervention group was increased (p=0.07).

(4) Sensation when the Amount of Intake was 120 mg Per Day

In the intervention group, the score of subjective symptom was significantly decreased in item of “I feel my eyes dry (after VDT load test)” of questionnaire at the sixth week after taking the extract (p=0.018).

(5) Schirmer's Test when the Amount of Intake was 160 mg Per Day

In the intervention group, the length of wet part of the test paper was increased 11.3% in left eye, 50.2% in right eye, and 20.6 as the average.

On the other hand, in the placebo group, the length of wet part of the test paper was decreased 52.2% in left eye, 21.9% in right eye, and 40.0% as the average, at the sixth week after taking the placebo capsules.

By comparison between the two groups at sixth week after taking the extract, the amount of lachrymal fluid of right eye of the intervention group was significantly increased, compare to the placebo group (p=0.024).

Though similar trend could not be found at the average of right eye and left eye, it was confirmed that the amount of lachrymal fluid of the intervention group was increased (p=0.071), compare to the placebo group.

(6) Sensation of Dryness of Eye when the Amount of Intake is 160 mg Per Day

The score of subjective symptom of intervention group was significantly decreased (p=0.044) in item of “I feel dryness of eye (after VDT work)” of questionnaire of at the sixth week after taking the extracts.

(7) Effect of Improvement of Stiff Neck and Shoulder when the Amount of Intake is 120 mg Per Day

The score of subjective symptom of intervention group was significantly decreased (placebo group: 4.5±1.8, interventional group: 3.4±1.0, p=0.09) in item of “I feel dryness of eye (after VDT work)” of questionnaire at 6th week after taking the extract.

(8) Effect of the Improvement of Stiff Neck and Shoulder when the Amount of Intake is 160 mg Per Day

Further, the score after intake was significantly decreased in the item “I feel stiff neck and shoulder (before VDT test)” of the questionnaire.

Further, the score of subjective symptom of intervention group was significantly decreased (p=0.004) at sixth week after taking the extract, compare to the placebo group.

Additionally, in item of “I feel stiff neck and shoulder (after VDT load test)” of questionnaire of subjective symptom, the score of the intervention group was significantly decreased after taking the extract (p=0.038).

Moreover, the score of the intervention group was significantly decreased compare to the placebo group at sixth week after taking the extract (p=0.029).

(Particle Size Distribution of Freeze-Dried Composition)

Particle size distribution of freeze-dried composition was confirmed.

Here, bilberry fruit extract was obtained by same way of the above-identified (1), and freeze-dried the bilberry fruit extracts so that the concentration of solid content was 10 wt % or 30 wt %, respectively.

As a result, it was found that the minimum particle diameter is 0.159 μm at 10 wt %, and 10% particle diameter (d10) was 3.29 μm. Thus, it was confirmed that the diameters were very small.

Further, at 30 wt %, the minimum particle diameter is 0.159 μm and 10% particle diameter (d10) is 2.76 μm. It is confirmed that the diameter is extremely small.

On the other hand, in the case of spray drying, the minimum diameter is 0.63 μm, the 10% particle diameter (d10) is 6.86 μm. the diameters were large.

This means that in the case of bilberry fruit extract, it is possible to obtain smaller particles without decomposition of active ingredient by freeze-drying.

This also means that the extract can be taken in the body with smaller particle diameter, and the transfer rate to eye will be high.

By the above test, it is confirmed that it is possible to obtain a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and/or stiff neck and shoulder, which contains bilberry fruit extract and is effective with less intake.

Especially, as transition rate of the anthocyanin of the above experiment derived from bilberry is high, and it is possible to transfer anthocyanin to eyes effectively and obtain high effect. 

What is claimed is:
 1. A composition for prevention and/or improvement of dry eye syndrome or dryness of eye, which comprises freeze-dried bilberry fruit extract.
 2. The composition according to claim 1, wherein said freeze-dried bilberry fruit extract comprises anthocyanin which is extracted from bilberry of 30% or more and 50% or less.
 3. The composition according to claim 1, wherein the amount of intake is 120 mg per day or more and 500 mg per day or less.
 4. A composition for prevention and/or improvement of stiff neck and shoulder, which comprises freeze-dried bilberry fruit extract.
 5. The composition according to claim 4, wherein said freeze-dried bilberry fruit extract contains anthocyanin which is extracted from bilberry of 30% or more and 50% or less.
 6. The composition according to claim 4, wherein the amount of intake is 120 mg per day or more and 500 mg per day or less.
 7. A composition for prevention and/or improvement of dry eye syndrome, dryness of eye, and stiff neck and shoulder, which comprises freeze-dried bilberry fruit extract.
 8. The composition according to claim 7, wherein said freeze-dried bilberry fruit extract contains anthocyanin which is extracted from bilberry of 30% or more and 50% or less.
 9. The composition according to claim 7, wherein the amount of intake is 120 mg per day or more and 500 mg per day or less.
 10. A method for producing a composition for prevention and/or improvement of dry eye syndrome, dryness of eye and stiff neck and shoulder comprising: a step of obtaining bilberry extract from bilberry fruit by using water-containing ethanol, and a step of freeze-drying said bilberry extract. 